tbuckley/cabot-search huggingface dataset:
Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI
Authors: Michiel B de Ruiter, Paul F C Groot, Sabine Deprez, Pim Pullens, Stefan Sunaert, Dirk de Ruysscher, Sanne B Schagen, José Belderbos
Journal: Neuro-Oncology (2022)

Abstract Background Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally, we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline. Methods High-quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated for 4 months (57 HA-PCI patients and 46 PCI patients) and 12 months (28 HA-PCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test–Revised (HVLT-R). Results HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions in gray matter and normal-appearing white matter, increases in white matter hyperintensities, and brain aging. There were no significant associations between hippocampal atrophy and memory. Conclusions HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.
Correction: PERK reprograms hematopoietic progenitor cells to direct tumor-promoting myelopoiesis in the spleen
Authors: Mingyu Liu, Chong Wu, Shufeng Luo, Qiaomin Hua, Hai-Tian Chen, Yulan Weng, Junyu Xu, Huiling Lin, Lu Wang, Jinheng Li, Lan Zhu, Zhenhong Guo, Shi-Mei Zhuang, Tiebang Kang, Limin Zheng
Journal: The Journal of Experimental Medicine (2022)
Abstract 5805: Novel approach to thymidylate synthase genotype determination and utility as a biomarker of severe toxicity to 5-FU chemotherapy
Authors: Huixing Huang, Dominic Schaerer, Remington Schmidt, Ting Zhang, Tanja K Froehlich, Kelly Bouchonville, Robert B Diasio, Ursula Amstutz, Carlo Largiadèr, Steven M Offer
Journal: Cancer Research (2022)

Abstract The primary mechanism of action for the chemotherapeutic 5-fluorouracil (5-FU) is inhibition of thymidylate synthase (TS), which leads to nucleotide imbalance and subsequent cellular death. Expression of TS has been suggested to be determined by a variable number of tandem repeats located within the TS enhancer region (TSER). TSER genotype has been inconsistently linked to 5-FU-related adverse events, including severe grade ≥3 drug-related toxicity. Our recent studies demonstrated that the number of repeats within the TSER, as well as the presence or absence of a polymorphism within each repeat, was significantly associated with 5-FU toxicity in 629 patients. Our findings are consistent with a model in which the number of upstream stimulatory factor (USF1) transcription factor binding sites in the TSER, which is determined both by repeat status and genotype within each repeat, defines TYMS expression and contributions to 5-FU toxicity risk. We present an updated nomenclature that concisely and unambiguously identifies both the number of repeats and the number of USF1 binding sites. The difficulty in obtaining clear genotypes within this highly repetitive and variable region limits the ability to integrate this biomarker into predictive tests. We present methodologies for assigning TSER genotypes using conventional and high-throughput sequencing, including whole genome sequence data. Our results are expected to promote the improved study of TSER genotype in future clinical studies and the integration of TSER status into clinical predictive tests for severe 5-FU toxicity. Citation Format: Huixing Huang, Dominic Schaerer, Remington Schmidt, Ting Zhang, Tanja K Froehlich, Kelly Bouchonville, Robert B Diasio, Ursula Amstutz, Carlo Largiadèr, Steven M Offer. Novel approach to thymidylate synthase genotype determination and utility as a biomarker of severe toxicity to 5-FU chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5805.
Modern Treatment of Asymptomatic Carotid Stenosis—The Importance of Both Medical Therapy and Carotid Endarterectomy
Authors: Alik Farber
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials
Authors: Andre Esteva, Jean Feng, Douwe van der Wal, Shih-Cheng Huang, Jeffry P. Simko, Sandy DeVries, Emmalyn Chen, Edward M. Schaeffer, Todd M. Morgan, Yilun Sun, Amirata Ghorbani, Nikhil Naik, Dhruv Nathawani, Richard Socher, Jeff M. Michalski, Mack Roach, Thomas M. Pisansky, Jedidiah M. Monson, Farah Naz, James Wallace, Michelle J. Ferguson, Jean-Paul Bahary, James Zou, Matthew Lungren, Serena Yeung, Ashley E. Ross, Michael Kucharczyk, Luis Souhami, Leslie Ballas, Christopher A. Peters, Sandy Liu, Alexander G. Balogh, Pamela D. Randolph-Jackson, David L. Schwartz, Michael R. Girvigian, Naoyuki G. Saito, Adam Raben, Rachel A. Rabinovitch, Khalil Katato, Howard M. Sandler, Phuoc T. Tran, Daniel E. Spratt, Stephanie Pugh, Felix Y. Feng, Osama Mohamad
Journal: npj Digital Medicine (2022)

Prostate cancer is the most frequent cancer in men and a leading cause of cancer death. Determining a patient's optimal therapy is a challenge, where oncologists must select a therapy with the highest likelihood of success and the lowest likelihood of toxicity. International standards for prognostication rely on non-specific and semi-quantitative tools, commonly leading to over- and under-treatment. Tissue-based molecular biomarkers have attempted to address this, but most have limited validation in prospective randomized trials and expensive processing costs, posing substantial barriers to widespread adoption. There remains a significant need for accurate and scalable tools to support therapy personalization. Here we demonstrate prostate cancer therapy personalization by predicting long-term, clinically relevant outcomes using a multimodal deep learning architecture and train models using clinical data and digital histopathology from prostate biopsies. We train and validate models using five phase III randomized trials conducted across hundreds of clinical centers. Histopathological data was available for 5654 of 7764 randomized patients (71%) with a median follow-up of 11.4 years. Compared to the most common risk-stratification tool-risk groups developed by the National Cancer Center Network (NCCN)-our models have superior discriminatory performance across all endpoints, ranging from 9.2% to 14.6% relative improvement in a held-out validation set. This artificial intelligence-based tool improves prognostication over standard tools and allows oncologists to computationally predict the likeliest outcomes of specific patients to determine optimal treatment. Outfitted with digital scanners and internet access, any clinic could offer such capabilities, enabling global access to therapy personalization.
Abstract 3688: Survival benefit of adjuvant radiotherapy among women with high comorbidity burden and low-risk breast cancer: SEER-MHOS analysis
Authors: Eunkyung Lee, Robert B. Hines, Jianbin Zhu, Kayla Montan, Michael J. Rovito
Journal: Cancer Research (2022)

Abstract Background: The National Comprehensive Cancer Network Breast Cancer Guidelines Committee has suggested that adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) could be omitted among older women with low-risk breast cancer (early-stage, node-negative, and ER-positive) if they were treated with endocrine therapy. However, the effect of RT among older women with multimorbidity is not clearly understood. Objective: We examined the effect of adjuvant RT on survival outcomes among older women. We also assessed whether the association between RT and survival is modified by comorbidity burden. Methods: A total of 1105 older women (65+) diagnosed with low-risk breast cancer in 1998-2012 and who received BCS were identified from the population-based Surveillance, Epidemiology, and End-Results-Medicare Health Outcomes Survey (SEER-MHOS) data resource. A propensity score-based inverse probability of treatment weight (IPTW) was calculated with weighting applied to Cox regression models to obtain hazard ratios for the association of RT with survival outcomes. Stratified analysis was conducted to examine differential effects according to the comorbidity burden class, which was identified using the latent class analysis. Results: Over a 5-year follow-up period, a total of 117 deaths occurred (25 cancer-related and 92 noncancer-related). The IPTW-adjusted Cox proportional hazard analysis showed that RT omission did not significantly increase the risk for 5-year cancer-specific deaths (P=0.202). However, RT omission increased the risk for 5-year noncancer death by 1.84-fold (95% CI=1.35, 2.51) and all-cause death by 1.49-fold (95% CI=1.41, 1.95). The stratified analysis showed that the effect of RT omission on the risk of breast cancer-specific deaths was similar across the different comorbidity groups. For noncancer and all-cause deaths, the effect of RT omission varied by comorbidity burden. In Class 1, RT omission was not associated with an increased risk of noncancer and all-cause deaths. However, in Classes 2 and 3, RT omission is significantly associated with an increased risk of 5-year all-cause deaths in a dose-response manner: by 1.66-fold (95% CI=1.07, 2.56) in Class 2 and 1.96-fold in Class 3 (95% CI=1.13, 3.41). Similar results were observed for 10-year survival. Conclusions: RT omission does not increase the risk of cancer-specific death and appears to be a valid clinical decision for older women with low-risk breast cancer and multimorbidity. Citation Format: Eunkyung Lee, Robert B. Hines, Jianbin Zhu, Kayla Montan, Michael J. Rovito. Survival benefit of adjuvant radiotherapy among women with high comorbidity burden and low-risk breast cancer: SEER-MHOS analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3688.
Screening for Impaired Visual Acuity in Older Adults
Authors: Anne L. Coleman, Stephen D. McLeod
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Does motor control training improve pain and function in adults with symptomatic lumbar disc herniation? A systematic review and meta-analysis of 861 subjects in 16 trials
Authors: Mohammadreza Pourahmadi, Somayeh Delavari, Jill A Hayden, Abbasali Keshtkar, Maryam Ahmadi, Azadeh Aletaha, Maryam Nazemipour, Mohammad Ali Mansournia, Sidney M Rubinstein
Journal: British Journal of Sports Medicine (2022)

To evaluate the effectiveness of motor control training (MCT) compared with other physical therapist-led interventions, minimal/no intervention or surgery in patients with symptomatic lumbar disc herniation (LDH).
Abstract 5190: Case report: long-term response to combination of Sintilimab, Bevacizumab and chemotherapy in a heavily pretreated refractory colon cancer patient with microsatellite stability
Authors: Zhi Cui, Qi Wang, Muhong Deng, Erhong Meng, Sheng Liu, Quanli Han
Journal: Cancer Research (2022)

Abstract Background: Unlike patients with advanced colorectal cancer (CRC) with deficient DNA mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors, most patients with advanced CRC with proficient DNA mismatch repair or microsatellite-stability (pMMR/MSS) tumors are not sensitive to immune checkpoint inhibitor (ICI) therapy. The current challenge is to find out innovative therapeutic combinations with ICIs for such patients. Case Presentation: In this study, we report a case of heavily pretreated refractory colon cancer with MSS but high-tumor mutation burden (TMB-H) tumors. After experiencing five lines of therapy, including chemotherapy and targeted therapy with anti-angiogenic inhibitor as well as anti-EGFR antibody, she received sixth-line therapy with combination of Sintilimab, Bevacizumab and chemotherapy, and obtained a durable clinical benefit. The patient’s progression-free survival (PFS) of sixth line therapy was about 9 months and overall survival (OS) has been over 4.6 years. Conclusion: To the best of our knowledge, this study represented the longest PFS of response to combination of ICI with other agents with different mechanisms of action in a heavily pretreated refractory colon cancer patient with MSS. Citation Format: Zhi Cui, Qi Wang, Muhong Deng, Erhong Meng, Sheng Liu, Quanli Han. Case report: long-term response to combination of Sintilimab, Bevacizumab and chemotherapy in a heavily pretreated refractory colon cancer patient with microsatellite stability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5190.
Investing in late-stage clinical trials and manufacturing of product candidates for five major infectious diseases: a modelling study of the benefits and costs of investment in three middle-income countries
Authors: Marco Schäferhoff, Armand Zimmerman, Mohamed M Diab, Wenhui Mao, Vipul Chowdhary, Davinder Gill, Robert Karanja, Mziwandile Madikizela, Osondu Ogbuoji, Gavin Yamey
Journal: The Lancet Global Health (2022)

BackgroundInvesting in late-stage clinical trials, trial sites, and production capacity for new health products could improve access to vaccines, therapeutics, and infectious disease diagnostics in middle-income countries. This study assesses the case for such investment in three of these countries: India, Kenya, and South Africa.MethodsWe applied investment case modelling and assessed how many cases, deaths, and disability-adjusted life years (DALYs) could be averted from the development and manufacturing of new technologies (therapeutics and vaccines) in these countries from 2021 to 2036, for five diseases—HIV, tuberculosis, malaria, pneumonia, and diarrhoeal diseases. We also estimated the economic benefits that might accrue from making these investments and we developed benefit–cost ratios for each of the three middle-income countries. Our modelling applies two investment case perspectives: a societal perspective with all costs and benefits measured at the societal level, and a country perspective to estimate how much health and economic benefit accrues to each middle-income country for every dollar invested in clinical trials and manufacturing by the middle-income country government. For each perspective, we modelled two scenarios: one that considers only domestic health and economic benefits; and one that includes regional health and economic benefits. In the regional scenarios, we assumed that new products developed and manufactured in India would benefit eight countries in south Asia, whereas new products developed and manufactured in Kenya would benefit all 21 countries in the Common Market for Eastern and Southern Africa (COMESA). We also assumed that all 16 countries in the Southern African Development Community (SADC) would benefit from products developed and manufactured in South Africa.FindingsFrom 2021 to 2036, product development and manufacturing in Kenya could avert 4·44 million deaths and 206·27 million DALYs in the COMESA region. In South Africa, it could prevent 5·19 million deaths and 253·83 million DALYs in the SADC region. In India, it could avert 9·76 million deaths and 374·42 million DALYs in south Asia. Economic returns would be especially high if new tools were produced for regional markets rather than for domestic markets only. Under a societal perspective, regional returns outweigh investments by a factor of 20·51 in Kenya, 33·27 in South Africa, and 66·56 in India. Under a country perspective, the regional benefit–cost ratios amount to 60·71 in India, 8·78 in Kenya, and 11·88 in South Africa.InterpretationOur study supports the creation of regional hubs for clinical trials and product manufacturing compared with narrow national efforts.FundingBill & Melinda Gates Foundation.
Abstract 2946: Perturb-seq analysis of TNFα-induced transcriptional response
Authors: Donato Tedesco, Alex Chenchik, Tianbing Liu, Dongfang Hu, Nadya Isachenko, Nadia Dolganov
Journal: Cancer Research (2022)

Abstract We performed a single-cell Perturb-seq screen on HEK293 cells with a ~100 sgRNA pooled library, aimed at identifying genes involved in TNFα-induced transcriptional response. As a reference, a parallel screen was performed with cells transduced in arrayed format with the same set of sgRNAs as the pooled library. For the pooled library screen, cells were transduced with the pooled sgRNA library, selected and expanded for 10 days, split into 2 samples for 72h TNFα treatment/mock-treatment. After treatment, cells were loaded on the 10X Genomics instrument according to manufacturer’s specifications at 2000, 7500 and 15,000 cells/sample/lane. For the arrayed screen, cells were transduced with individual sgRNAs in arrayed format, selected and expanded for 10 days, split into 2 samples for 72h TNFα treatment/mock treatment. After treatment ~10,000 from each sample were harvested for RNA purification. For both pooled library single-cell and arrayed screens, genome-wide transcriptome analysis was assayed using the DriverMap Targeted RNA-Seq assay. Both screens identified TNFRSF1A and IKBKG as top mediators of TFNα transcriptional response. Citation Format: Donato Tedesco, Alex Chenchik, Tianbing Liu, Dongfang Hu, Nadya Isachenko, Nadia Dolganov. Perturb-seq analysis of TNFα-induced transcriptional response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2946.
Abstract 501: Acute kidney injury induced by allogeneic hematopoietic stem cell transplantation: disease understanding and treatment with nanotechnology-based therapeutics
Authors: Magdalini Panagiotakopoulou, Emma Grabarnik, Edgar A. Jaimes, Marcel R. van den Brink, Daniel A. Heller
Journal: Cancer Research (2022)

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a highly effective treatment for a variety of hematologic malignancies, but also associated with serious complications, such as graft-versus-host-disease (GVHD), a severe immune condition that manifests in multiple organs including the kidneys. Kidney injury in the setting of allo-HSCT has an incidence as high as 80% and leads to high patient morbidity and mortality, however, its progression and mechanisms remain poorly characterized. Moreover, no approved drugs for AKI of any etiology exist, as most experimental therapies have poor pharmacokinetic profiles and minimal efficacy in treating AKI in humans. We have characterized the pathology, genetic and molecular signatures of GVHD-mediated AKI in a murine model of HCT. GVHD results in AKI characterized predominantly by T-cell infiltration and activation of inflammatory pathways in both donor infiltrating inflammatory cells, as well as resident cells (i.e. tubules). By RNA sequencing, we have identified specific inflammatory pathways that are differentially expressed between healthy and GVHD mice and can serve as targets for therapeutic intervention. Moreover, we have synthesized nanoparticles that can specifically target proteins overexpressed in GVHD-kidneys and can encapsulate a variety of small molecule drugs. The complete understanding of this disease and development of this technology has a high potential to improve clinical practice and patient prognosis after allo-HCT, but it can also serve as a platform for treating other forms of cancer-associated kidney injury (e.g. induced by nephrotoxic chemotherapy), thus affecting the life of numerous patients. Citation Format: Magdalini Panagiotakopoulou, Emma Grabarnik, Edgar A. Jaimes, Marcel R. van den Brink, Daniel A. Heller. Acute kidney injury induced by allogeneic hematopoietic stem cell transplantation: disease understanding and treatment with nanotechnology-based therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 501.